Circulating Adiponectin and Omentin Across Cardiometabolic Phenotypes: Links to Atherogenic Indices in Prediabetes and New-Onset Type 2 Diabetes

Adiponectin and omentin are adipose tissue-derived adipokines implicated in insulin sensitivity and cardiometabolic regulation. Their behavior across different stages of dysglycemia, as well as in relation to visceral adiposity and cardiometabolic phenotypes, remains incompletely understood. In this cross-sectional study, circulating adiponectin and omentin levels were evaluated in individuals with prediabetes (PreDM, <i>n</i> = 100) and newly diagnosed type 2 diabetes mellitus (T2DM, <i>n</i> = 128). Associations with insulin resistance-related indices, including the triglyceride-glucose (TyG) index and TyG-derived composites, the visceral adiposity index (VAI), cardiometabolic phenotypes, and cardiovascular risk categories, were assessed using correlation and multivariable regression analyses. Discriminatory performance for metabolically unhealthy obesity was evaluated using receiver operating characteristic (ROC) curve analysis. Both adiponectin and omentin levels were lower in T2DM compared with PreDM (22.05 vs. 30.30 and 25.72 vs. 38.84, <i>p</i> < 0.0001 for both). In PreDMs, omentin showed a significant inverse correlation with the TyG index (weak correlation, <i>ρ</i> = -0.197, <i>p</i> = 0.050), whereas adiponectin demonstrated only weak trends. In multivariable models, VAI and male sex were independent predictors of circulating omentin levels, whereas fasting insulin was not. In contrast, adiponectin did not retain independent associations with metabolic or visceral adiposity indices. In T2DM, adipokine-metabolic associations were largely absent. Neither adipokine differed substantially across cardiometabolic phenotypes or cardiovascular risk categories. ROC analyses revealed modest overall discriminatory performance for metabolically obese phenotypes, with poor discrimination after stratification by glycemic status (area under the ROC curve (AUC) of 0.704 for adiponectin and 0.710 for omentin, and AUC of 0.431 for adiponectin and 0.461 for omentin, respectively). Circulating adipokines appear to exhibit stage-dependent relationships with metabolic dysfunction, being more informative in PreDM than in established T2DM. Omentin may reflect visceral adiposity-related metabolic alterations in early dysglycemia, whereas adiponectin shows limited independent associations. Overall, these findings suggest that adipokines have limited diagnostic or cardiovascular risk-stratification utility when considered in isolation and may be better interpreted within multimarker cardiometabolic assessment frameworks.